It is well recognized that HIV infection results in decline in nervous system function over time, and there have been a number of studies evaluating this effect. These are essentially limited to the study of infected males,a nd there has been a distressing lack of research on nervous system effects in females. Our own preliminary studies and reports of others suggests that there may be a differential effect of HIV infection in males and females, with females showing a more rapid decline in central nervous system function. The cause of the effects of HIV on the nervous system in poorly understood, although there is reason to believe that it may be related to both altered immunological function and viral burden. It is well recognized that there are significant differences in the responses of female and male immune systems to a variety of challenges. It is possible that differential immunological responses and viral burden may play a role in gender differences in disease progression. We hypothesize that; 1. In HIV infection, there will be a differential rate of progression of nervous system disease between females and males, 2. There is a direct correlation between the development and progression of nervous system disease and the level of circulating viral burden in HIV infected females and males; 3. There is a direct correlation between the differential progression of nervous system dysfunction and immune dysfunction in females and males with HIV infection. In this project we propose to study three cohorts 1) HIV infected females; 2) HIV infected males; 3) uninfected females. We will use a number of highly sensitive studies to monitor a) nervous system function; b) immune status; c) viral burden in blood and cerebrospinal fluid. Each cohort will contain 50 subjects matched for route of infection, drug use, education, age, immune status at entry. Progression will be studied over five years. This study is linked to an RO-1 to study MRS and MRI, and an RO-3 to study sleep disruption, both in the same population.